Methods to administer ethinyl estradiol and prodrugs thereof with improved bioavailability

Abstract

Methods of improving the bioavailability of ethinyl estradiol by orally administering to a patient a solid dosage form containing ethinyl estradiol or prodrug thereof where that dosage form releases at least some of the ethinyl estradiol or prodrug thereof in the oral cavity for absorption through the oral mucosa to treat the patient for a predetermined indication such as, for example, hormone replacement therapy or contraception. The solid dosage forms may be selected from, among others, chewable tablets, fast melt tablets, films, dissolving films, mucoadhesive tablets, lozenges, and chewing gum.

1 . A method of administering ethinyl estradiol or a prodrug thereof to a patient with improved bioavailability comprising the step of orally administering a solid dosage form containing ethinyl estradiol or the prodrug thereof that releases an effective amount of the ethinyl estradiol or the prodrug thereof in the oral cavity for absorption through the oral mucosa to treat the patient for a predetermined indication and wherein the patient is instructed to orally administer the solid dosage form with about 2 ounces of water or less. 
     
     
         2 . The method according to  claim 1 , wherein at least about 15 percent of the ethinyl estradiol or prodrug thereof contained in the oral solid dosage form is absorbed through the oral mucosa. 
     
     
         3 . The method according to  claim 1 , wherein the patient is instructed to orally administer the solid dosage form without taking water therewith. 
     
     
         4 . The method according to  claim 1 , wherein the patient is a female and the predetermined indication is oral contraception. 
     
     
         5 . The method according to  claim 1 , wherein the predetermined indication is hormone replacement therapy. 
     
     
         6 . The method according to  claim 1 , wherein the solid dosage form is selected from the group consisting of a chewable tablets, orally disintegrating tablets, films, dissolving films, mucoadhesive tablets, lozenges and chewing gum. 
     
     
         7 . The method according to  claim 1 , wherein the dosage form is a chewable tablet and the patient is instructed to chew the tablet prior to swallowing. 
     
     
         8 . The method according to  claim 7 , wherein the patient is further instructed to orally administer the chewable tablet without taking water therewith. 
     
     
         9 . The method according to  claim 7 , wherein the patient is further instructed to orally administer the chewable tablet with 2 ounces or less of water. 
     
     
         10 . The method according to  claim 1 , wherein the dosage form comprises ethinyl estradiol with progestogen in an amount effective for oral contraception in a female patient. 
     
     
         11 . The method according to  claim 1 , wherein the dosage form comprises ethinyl estradiol with progestogen in an amount effective for treatment of symptoms of menopause. 
     
     
         12 . The method according to  claim 10 , wherein the dosage form is a chewable tablet. 
     
     
         13 . The method according to  claim 11 , wherein the dosage form is a chewable tablet. 
     
     
         14 . The method according to  claim 12 , wherein the dosage form comprises about 0.5 μg to about 50 μg of ethinyl estradiol. 
     
     
         15 . The method according to  claim 13 , wherein the dosage form comprises about 0.5 μg to about 50 μg of ethinyl estradiol. 
     
     
         16 . The method according to  claim 14 , wherein the dosage form comprises about 0.3 mg to about 1.5 mg of norethindrone acetate or norethindrone. 
     
     
         17 . The method according to  claim 15 , wherein the dosage form comprises about 0.3 mg to about 1.5 mg of norethindrone acetate or norethindrone. 
     
     
         18 . The method according to  claim 1 , wherein the dosage form is administered once daily. 
     
     
         19 . The method according to  claim 1 , wherein the dosage form is an orally disintegrating tablet. 
     
     
         20 . The method according to  claim 1 , wherein the solid dosage form is a chewable tablet comprising: (i) about 0.5 to about 50 μg of ethinyl estradiol; (ii) about 0.3 mg to about 1.5 mg of norethindrone acetate or norethindrone; and (iii) about 10% to about 95% by weight of an oral dissolution enhancing carrier selected from the group consisting of lactose, corn starch, maltodextrin, dextrose, mannitol, sorbital, xylitol, fructose, sucrose or mixtures thereof. 
     
     
         21 . The method according to  claim 17 , wherein the oral dissolution enhancing carrier is present in an amount of 30% to about 90% by weight of the solid dosage form. 
     
     
         22 . The method according to  claim 18 , wherein the oral dissolution enhancing carrier is mannitol. 
     
     
         23 . The method according to  claim 19 , wherein the mannitol is present in an amount of about 40% to about 80% by weight of the composition. 
     
     
         24 . An orally administered solid dosage form capable of delivering ethinyl estradiol with improved bioavailability to a patient in need thereof, said solid dosage form comprising: (i) about 0.5 μg to about 50 μg of ethinyl estradiol and (ii) an oral dissolution enhancing carrier that provides for at least 15% absorption of the ethinyl estradiol through the oral mucosa when said solid dosage form is orally administered to the patient with 2 ounces of water or less. 
     
     
         25 . The solid dosage form of  claim 24 , wherein the solid dosage form is a chewable tablet and the oral dissolution enhancing carrier is present in an amount of about 10% to about 95% by weight of the solid dosage form and is selected from the group consisting of lactose, corn starch, maltodextrin, dextrose, mannitol, sorbitol, xylitol, fructose, sucrose or mixtures thereof. 
     
     
         26 . The solid dosage form of  claim 25 , further comprising norethindrone acetate or noerthindrone in an amount of about 0.3 mg to about 1.5 mg.